NCT06393374招募中3 期
A Phase 3, Randomized, Open-label, Study to Compare the Efficacy and Safety of Adjuvant MK-2870 in Combination With Pembrolizumab (MK-3475) Versus Treatment of Physician's Choice (TPC) in Participants With Triple-Negative Breast Cancer (TNBC) Who Received Neoadjuvant Therapy and Did Not Achieve a Pathological Complete Response (pCR) at Surgery
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,530
- 试验地点
- 582
- 主要终点
- Invasive Disease-Free Survival (iDFS)
研究概览
简要总结
This is a randomized, open-label study comparing the efficacy and safety of adjuvant sacituzumab tirumotecan (MK-2870) in combination with pembrolizumab compared to treatment of physician's choice (TPC) in participants with triple-negative breast cancer (TNBC) who received neoadjuvant therapy and did not achieve a pathological complete response (pCR) at surgery. The primary objective is to compare sacituzumab tirumotecan plus pembrolizumab to TPC (pembrolizumab or pembrolizumab plus capecitabine) with respect to invasive disease-free survival (iDFS) per investigator assessment. It is hypothesized that sacituzumab tirumotecan plus pembrolizumab is superior to TPC with respect to iDFS per investigator assessment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has centrally confirmed TNBC, as defined by the most recent American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines
- •Has no evidence of locoregional or distant relapse, as assessed by the treating physician
- •Had neoadjuvant treatment based on the KEYNOTE-522 regimen (pembrolizumab with carboplatin/taxanes and pembrolizumab with anthracycline-based chemotherapy) followed by surgery according to National Comprehensive Cancer Network (NCCN) treatment guidelines for TNBC
- •Had adequate excision and surgical removal of all clinically evident disease in the breast and/or lymph nodes and have adequately recovered from surgery
- •Has non-pathologic complete response at surgery
- •Is able to continue on adjuvant pembrolizumab
- •Randomization must be conducted within 16 weeks from surgical resection
- •Completed adjuvant radiation therapy (if indicated) and recovered before randomization
- •Has provided tissue from the surgical resection for central laboratory determination of trophoblast cell surface antigen 2 (TROP2) status
- •If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention (120 days for sacituzumab tirumotecan and 95 days for capecitabine [no restriction for pembrolizumab]): agrees to refrain from donating sperm AND is either abstinent and agrees to remain abstinent or uses highly effective contraception
- •For females (assigned at birth), is not pregnant or breastfeeding and ≥1 of the following applies: is not a participant of childbearing potential (POCBP) OR is a POCBP and uses highly effective contraception after the last dose of study intervention (210 days for sacituzumab tirumotecan, 120 days for pembrolizumab, and 185 days for capecitabine). Abstains from breastfeeding during the study intervention period and for at least 120 days after study intervention
- •Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline (except alopecia)
- •Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
- •An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before first dose of study treatment
- •Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B birus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization
排除标准
- •Has a known germline breast cancer gene (BRCA) mutation (deleterious or suspected deleterious) and is eligible for adjuvant therapy with olaparib where olaparib is approved and available
- •Has Grade >2 peripheral neuropathy
- •History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
- •Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
- •Has uncontrolled, significant cardiovascular disease or cerebrovascular disease including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to >480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months prior to study intervention
- •Received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)-directed antibody drug conjugate (ADC) or a topoisomerase I inhibitor-containing ADC
- •Received anticancer therapy in the adjuvant phase including but not limited to chemotherapy, small molecule anticancer drugs, poly (adenosine diphosphate ribose) polymerase (PARP) inhibitors, ADCs, and/or immunotherapy, with the exception of adjuvant radiation therapy
- •Is currently receiving a strong inducer/inhibitor of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study. The required washout period before starting sacituzumab tirumotecan is 2 weeks
- •Except for pembrolizumab as neoadjuvant therapy for early-stage TNBC: received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein-4 [CTLA-4], OX-40 [cluster of differentiation (CD) 134], or CD137)
- •Except for chemotherapy as neoadjuvant therapy for early-stage TNBC: Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization
- •Received prior radiotherapy within 3 weeks of start of study intervention or required corticosteroids for radiation related toxicities that cannot be discontinued before the first dose of study intervention
- •Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed
- •Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
- •Has known additional malignancy that is progressing or has required active treatment within the past 5 years
- •Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
- •Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
- •Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- •Has active infection requiring systemic therapy
- •HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Has concurrent active hepatitis B and hepatitis C virus infection
- •Has history of allogeneic tissue/solid organ transplant
研究组 & 干预措施
Pembrolizumab + sacituzumab tirumotecan
Experimental
Participants receive pembrolizumab every 6 weeks (q6w) in combination with sacituzumab tirumotecan every 2 weeks (q2w) for 24 weeks. In addition, participants receive an antihistamine, an H2 antagonist of investigator's choice, acetaminophen (or equivalent), and dexamethasone (or equivalent) per each drug's product label prior to sacituzumab tirumotecan infusions.
干预措施: Pembrolizumab (Biological)
Treatment of Physician's Choice
Active Comparator
Participants receive pembrolizumab q6w or pembrolizumab q6w in combination with capecitabine (twice daily [BID] on Days 1 to 14 and 22 to 35 every 42 days x 4 [2 weeks 1, 1 week off]) for 24 weeks.
干预措施: Pembrolizumab (Biological)
Treatment of Physician's Choice
Active Comparator
Participants receive pembrolizumab q6w or pembrolizumab q6w in combination with capecitabine (twice daily [BID] on Days 1 to 14 and 22 to 35 every 42 days x 4 [2 weeks 1, 1 week off]) for 24 weeks.
干预措施: Capecitabine (Drug)
Pembrolizumab + sacituzumab tirumotecan
Experimental
Participants receive pembrolizumab every 6 weeks (q6w) in combination with sacituzumab tirumotecan every 2 weeks (q2w) for 24 weeks. In addition, participants receive an antihistamine, an H2 antagonist of investigator's choice, acetaminophen (or equivalent), and dexamethasone (or equivalent) per each drug's product label prior to sacituzumab tirumotecan infusions.
干预措施: Sacituzumab tirumotecan (Biological)
结局指标
主要结局
Invasive Disease-Free Survival (iDFS)
时间窗: Up to ~77 months
iDFS is the time from randomization to invasive local, regional, or distant recurrence, invasive contralateral breast cancer, or death due to any cause, whichever occurs first.
次要结局
- Overall Survival (OS)(Up to ~101 months)
- Distant recurrence-free survival (DRFS)(Up to ~101 months)
- Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score(Baseline and up to ~60 months)
- Change from baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score(Baseline and up to ~60 months)
- Change from baseline in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score(Baseline and up to ~60 months)
- Change from baseline in EORTC QLQ-C30 Fatigue (Items 10, 12, and 18) Combined Score(Baseline and up to ~60 months)
- Number of participants who experience one or more adverse events (AEs)(Up to ~42 weeks)
- Number of participants who discontinue study intervention due to an AE(Up to 24 weeks)
研究者
研究点 (582)
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